Abstract
The aim of this study is to elucidate the biogenetic modification of donor and recipient interleukin-28B (IL-28B) genotypes in liver graft biopsies after living donor liver transplantation (LDLT) for chronic hepatitis C virus- (HCV-) related, end-stage liver disease. Fifty liver graft biopsies were collected from recipients during LDLT treatment for HCV-related, end-stage liver disease. DNA was extracted from all 50 liver tissues, and the IL-28B single-nucleotide polymorphisms (SNPs) rs8099917 and rs12979860 were studied for allelic discrimination by real-time PCR analysis. Blood samples were obtained from donors and recipients on postoperative day 0 (POD0), POD7, and POD30. We randomly selected five liver biopsies and isolated the hepatocytes by laser capture microdissection (LCM) to evaluate genotype modifications resulting from LDLT. After LDLT, the IL-28B SNP rs8099917 was identified not only in the liver graft biopsies and donors' sera (TT = 41 : 43; GT = 9 : 5; GG = 0 : 2), but also in liver graft biopsies and recipients' sera on POD0 (TT = 41 : 44; GT = 9 : 4; GG = 0 : 2), POD7 (TT = 41 : 30; GT = 9 : 18; GG = 0 : 2), and POD30 (TT = 41 : 29; GT = 9 : 19; GG = 0 : 2). A significant difference was observed between the rs8099917 allele frequencies of liver graft biopsies and recipients' sera on POD30 (p = 0.039). In addition, a significant difference was also noted between the rs12979860 allele frequencies of liver graft biopsies and donors' sera (CT = 49 : 39; TT = 1 : 10) (p = 0.012) and of liver graft biopsies and recipients' sera on POD0 (CT = 49 : 39; TT = 1 : 11) (p = 0.002), POD7 (CT = 49 : 42; TT = 1 : 8) (p = 0.016), and POD30 (CT = 49 : 41; TT = 1 : 9) (p = 0.008). This phenomenon was confirmed by pyrosequencing of hepatocytes isolated by LCM. Following LDLT, the TT-to-GT IL-28B genotype modification predominated in rs8099917, and the CC-to-CT modification predominated in rs12979860. In conclusion, these modified phenomena suggested that the selected donor with a predictable and favourable IL-28B genotype will not confer a benefit on the recipient in the living donor liver transplantation setting.
Highlights
In hepatitis C virus (HCV) infection control, human interleukin 28B (IL-28B) genetics may play a role in patients’ selection and treatment decisions
DNA was extracted from all liver tissues, and IL-28B single-nucleotide polymorphisms (SNPs) rs8099917 and rs12979860 allele frequencies were studied by real-time polymerase chain reaction (PCR) analysis
We found that 54% (27/50) of the allografts presented with chronic hepatitis related to recurrent HCV infection with Ishak’s system- (ISHAK-) modified Histology Activity Index (HAI) necroinflammatory scores of 4 to 8 and ISHAKmodified fibrosis scores of 1 to 3
Summary
In hepatitis C virus (HCV) infection control, human interleukin 28B (IL-28B) genetics may play a role in patients’ selection and treatment decisions. Since the liver is the primary target organ and replication site of HCV, possible modification or dominant expression of IL-28B genotype has been confirmed in liver grafts after living donor liver transplantation (LDLT). A discrepancy in IL-28B genotypes between recipients and donor grafts and the related efficacy in preventing HCV recurrence after LDLT remain unelucidated. It is worth studying the effect of different IL-28B genotypes on HCV replication between donors and recipients after LDLT. We investigated the biogenetic modification of IL-28B SNPs rs8099917 and rs12979860 in liver graft biopsies and sera after LDLT. The current study would like to identify the evidence of the modification on IL-28B rs8099917 and rs12979860 in different genotypes of donor and recipients undergo LDLT
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